A substantial body of in vitro data indicates that parathyroid cells and C-cells respond specifically to a number of biogenic amines, including epinephrine, norepinephrine, dopamine, histamine and others. These compounds activate adenylate cyclase, increase cyclic AMP accumulation, and stimulate secretion of parathyroid hormone (PTH) and calcitonin (CT) independent of changes in ambient calcium concentration. Studies in vivo have not uniformly supported an important effect of these amines on PTH or CT release. The overall hypothesis to be tested in the proposed research is that biogenic amines have physiologic importance in non-ionic regulation of PTH and CT secretion in vivo. Particular attention will be paid to the possibility that the autonomic nervous system may influence the secretion of PTH and CT by stimulatory beta-adrenergic effects, and inhibitory alpha-adrenergic and cholinergic effects. Preliminary results obtained by the applicant support the concept that both chemical and electrical stimuli to autonomic nerves can increase PTH and CT secretion in dog and rat. Sensitive radioimmunoassays for canine and murine PTH, and murine CT are avilable in this laboratory. These tools will be used in conjunction with pharmacologic agonists and antagonists, electrostimulation of autonomic nerves, and chemical nerve ablation to explore the role of biogenic amines as controllers of PTH and CT release in rats and dogs. The definitive arrangements for collaboration with experts in biogenic amine physiology, neuropharmacology, and anesthesiology should assure success of the project. The proposed research will provide information about the physiologic importance of biogenic amines to calcium homeostasis, and guide us in the design of later studies to explore the role of these substances in human diseases of mineral metabolism.